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Neurogenetics
Published in: neurogenetics 4/2004

01-12-2004 | Original Article

Comprehensive association analysis of APOE regulatory region polymorphisms in Alzheimer disease

Authors: Kristin K. Nicodemus, Judith E. Stenger, Donald E. Schmechel, Kathleen A. Welsh-Bohmer, Ann M. Saunders, Allen D. Roses, John R. Gilbert, Jeffery M. Vance, Jonathan L. Haines, Margaret A. Pericak-Vance, Eden R. Martin

Published in: Neurogenetics | Issue 4/2004

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Abstract

Several recent case-control studies have examined the association between single nucleotide polymorphisms (SNPs) in the promoter region of the apolipoprotein E gene (APOE) and risk of Alzheimer disease (AD), with conflicting results. We assessed the relation between five APOE region SNPs and risk of AD in both case-control and family-based analyses. We observed a statistically significant association with the +5361T allele in the overall case-control analysis (P value=0.04) after adjusting for the known effect of the APOE-4 allele. Further analysis revealed this association to be limited to carriers of the APOE-4 allele. Age-stratified analyses in the patients with age at onset of 80 years or greater and age-matched controls showed that the −219T allele (P value=0.009) and the +113C allele (P value=0.03) are associated with increased risk of AD. Despite these findings, haplotype and family-based association analyses were unable to provide evidence that the APOE region SNPs influenced risk of AD independent of the APOE-4 allele. In addition to risk, we tested for association between the SNPs and age at onset of AD, but found no association in the case-control or family based analyses. In conclusion, SNPs +5361, or a SNP in strong linkage disequilibrium, may confer some additional risk for developing AD beyond the risk due to APOE-4; however, the effect independent of APOE-4 is likely to be small.
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Metadata
Title
Comprehensive association analysis of APOE regulatory region polymorphisms in Alzheimer disease
Authors
Kristin K. Nicodemus
Judith E. Stenger
Donald E. Schmechel
Kathleen A. Welsh-Bohmer
Ann M. Saunders
Allen D. Roses
John R. Gilbert
Jeffery M. Vance
Jonathan L. Haines
Margaret A. Pericak-Vance
Eden R. Martin
Publication date
01-12-2004
Publisher
Springer-Verlag
Published in
Neurogenetics / Issue 4/2004
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI
https://doi.org/10.1007/s10048-004-0189-9

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